These investigations are devoted to the development of non-invasive methods of accessing tissue structure and function. Two general techniques. are being developed: nuclear magnetic resonance (NMR) and optical spectroscopy/ imaging. Over the last year we have made the following developments in NMR technology: 1) We have further developed the theory and practical application of magnetization transfer contrast (MTC). This approach permits the imaging of the interaction rate between water and macromolecules in the body resulting in a unique form of high resolution image contrast and %issue characterization. We have utilized this approach in two regions of the human body, the knee joint and the heart. 2) Studies on a variety of macromolecules, as well as temperature and pH effects, reveal that this magnetization transfer contrast effect is a specific process depending on the surface chemistry and correlation times of the macromolecules. Surface hydroxyl groups are critically important. We speculate that the interaction involves a van der Waals type interaction between the water and the macromolecule. 3) Using a specialized NMR spectroscopy localization technique (SLOOP) the distribution of 3-fluorosorbitol production from 3-fluorodeoxyglucose via aldose reductase in the intact rabbit eye was collected. This study revealed that the aldose reductase activity in vivo is limited to the cortex of the lens. 4) A new approach to the study of isolated mitochondria was developed. This preparation permits the monitoring of NMR and optical data for over 12 hours under steady state conditions. These studies provided the first 13C NMR studies of mitochondrial metabolism. 5) The installation of a 4 Tesla 1 meter bore human NMR spectrometer has been initiated. The system is currently undergoing field testing but should be capable of NMR studies of human biochemistry and structure in the following year.